Exposure to damaging ionizing radiation can stem from various sources and pose significant health risks. For example, military forces and inhabitants of metropolitan areas are at risk of exposure from a nuclear or radiological attack, industrial accidents, and environmental pollution. Patients are often subjected to ionizing radiation in the course of medical care, including X-ray diagnoses and therapies for cell-proliferative disorders.
Depending on the level of exposure, the effects of radiation can range from nausea and vomiting, to immune system compromise, and to death from radiation-induced tissue damage or infection. Exposure to moderate doses of gamma radiation has been shown to cause chromosomal damage and defects in hematopoiesis and immunosuppression. Successively higher radiation doses compound these effects with gastrointestinal (GI) and neurovascular tissue damage.
Ionizing radiation can trigger free-radical reactions that lead to the formation of reactive oxygen species (ROS). It is generally believed that production of ROS is a primary mechanism underlying radiation-induced biological damage. The cells of the immune and blood-forming systems are particularly sensitive to changes in oxidant/antioxidant balance due to the high percentage of polyunsaturated fatty acids in their plasma membranes. The oxidant/antioxidant balance is thus an important determinant for both immune and blood-forming functions, not only for maintaining the integrity and function of the plasma membrane, cellular proteins, and nucleic acids, but also for control of signal transduction and gene expression.
The triage of suspected radiation over-exposed individuals is critical to determine those individuals requiring appropriate medical treatment. Early treatment of populations exposed to ionizing radiation requires accurate and rapid biodosimetry to determine an individual's exposure level and risk for morbidity and mortality. Tissue specific protein biomarkers detected in peripheral blood can provide diagnostic information of organ specific radiation injury to the medical community to effectively manage radiation casualty incidents. The small bowel is a major dose-limiting organ with regard to both acute and late treatment-related morbidity when abdominal or pelvic cancers are treated with radiotherapy. Small bowel irradiation results in epithelial cell loss and consequently impairs function and metabolism. Amino acid citrulline, a metabolic end product of small bowel enterocytes, can be used for quantifying radiation-induced epithelial cell loss.
Currently available methods to measure citrulline level in blood plasma are high-performance liquid chromatography (HPLC) and gas chromatography/mass spectrometry (GC/MS). These methods require skilled personnel and expensive equipment, long time, and high cost to analyze samples and are not suited for repeated measurements as a routine in daily clinical practice.
The present invention provides assays for assessing radiation induced injury and exposure. The assays may be applicable in daily clinical practice during the acute and late phases of radiation injury, so that the most effective treatment can be provided to the subject. Furthermore, the information provided by the assays is sufficient to help a clinician develop the best possible means of treatment for each subject individually and depending on their level of exposure.